Murat Mert Atmaca

Intravenous levetiracetam treatment in status epilepticus: A prospective study

OBJECTIVE To assess the efficacy of intravenous (IV) levetiracetam (LEV) in the treatment of status epilepticus (SE) and treatment outcomes. METHODS This study was conducted on patients, who were classified according to the clinical characteristics of their seizures, in the emergency department, neurology, and other services of our hospital. Patients were administrated IV LEV for the treatment of their SE after failing to respond to IV diazepam. RESULTS We prospectively investigated 30 patients, 16 females and 14 males whose ages ranged between 17 and 90 years (55.6 ± 19.6). Fourteen patients had convulsive SE (CSE), 11 had nonconvulsive SE (NCSE), and 5 had epilepsia partialis continua (EPC). The patients were given IV LEV with dosages ranging between 1000 and 4000 mg/day. Twenty-nine of the patients continued to receive LEV orally as maintenance treatment. The most common etiologies were cerebrovascular diseases (n = 7) and brain tumors (n = 6). SE was terminated in 23 (76.6%) patients. In the 12 months that followed SE, 9 of our patients (30%) died and 4 patients could not be contacted. Fifteen patients reported having no adverse effects, whereas three had mild adverse effects. No major adverse effects or complications causing disability were observed in twelve patients who were unconscious. CONCLUSION Treatment with IV LEV is well-tolerated and effective both in focal and generalized SE. IV LEV has the combined advantage of efficacy, safety, and ease of use, which qualifies it to be the first choice after benzodiazepines (BZD) in the treatment of SE. This is the first prospective study of IV LEV treatment in status epilepticus and has the longest follow-up period, one year.

Predictors of outcomes and refractoriness in status epilepticus: A prospective study

OBJECTIVE The objective of this study was to determine the predictors of outcomes and refractoriness in status epilepticus (SE). METHODS This is a prospective study of 59 adult patients with SE who were admitted to the Emergency Department between February 2012 and December 2013. The effects of clinical, demographic, and electrophysiologic features of patients with SE were evaluated. To evaluate outcome in SE, STESS, mSTESS, and EMSE scales were used. RESULTS Logistic regression analysis showed that being aged ≥65years (p=0.02, OR: 17.68, 95% CI: [1.6-198.4]) for the short term and having potentially fatal etiology (p=0.027, OR: 11.7, 95% CI: [1.3-103]) for the long term were the only independent predictors of poor outcomes; whereas, the presence of periodic epileptiform discharges (PEDs) in EEG was the only independent predictor of refractoriness (p=0.032, OR: 13.7, 95% CI: [1.3-148.5]). The patients with ≥3 Status Epilepticus Severity Score (STESS) did not have poorer outcomes in the short- (p=0.157) and long term (p=0.065). There was no difference between patients with 0-2, 3-4, and ≥4 mSTESS in the short- and long term in terms of outcome (p=0.28 and 0.063, respectively). Also, there was no difference between subgroups (convulsive SE [CSE], nonconvulsive SE [NCSE], and epilepsia partialis continua [EPC]) in terms of STESS and mSTESS. When patients with EPC were excluded, both STESS and mSTESS scores of the patients correlated with poorer long-term outcomes (p=0.025 and 0.017, respectively). The patients with ≥64 points in the Epidemiology-based Mortality in SE-Etiology, age, comorbidity, EEG (EMSE-EACE) score and those with ≥27 points in EMSE-Etiology, age, comorbidity (EMSE-EAC) score did not have poorer outcomes in the short term (p=0.06 and 0.274, respectively) while they had significantly poorer outcome in the long term (p<0.001 and 0.002, respectively). In subgroup analysis, patients with CSE with ≥64 points in EMSE-EACE had significantly poorer outcome in the both short- and long term (p=0.014 and 0.012, respectively), and patients with CSE with ≥27 points in EMSE-EAC had significantly poorer outcome in the long term (p=0.03) but not in the short term (p=0.186). Outcomes did not correlate with EMSE scores in patients with NCSE and EPC. Status epilepticus was terminated with intravenous (IV) levetiracetam (LEV) in 68.75% of patients and with IV phenytoin (PHT) in 83.3% of patients. No statistically significant difference was found between the two groups in terms of efficacy (p=0.334). CONCLUSION Being aged ≥65years predicts poor short-term outcomes, and having potentially fatal etiology predicts poor long-term outcomes, which highlight the importance of SE treatment management in the elderly. Both STESS and mSTESS are not predictive for poor outcomes in EPC. Excluding patients with EPC, STESS, and mSTESS could predict poor long-term outcomes but not in the short term in SE. Epidemiology-based Mortality in Status Epilepticus score could predict poor outcome in the long term better than STESS and mSTESS. Specifically, EMSE scores correlated with poor outcome in patients with CSE but not with NCSE and EPC. New scales are needed to predict outcome especially in patients with NCSE and EPC. The presence of PEDs in EEG is a predictor of RSE, and EMSE score can also be used to predict RSE. There was no difference in the efficacy of IV LEV and IV PHT in SE. This study is significant for having one of the longest follow-up periods in the literature.

Genotypic and phenotypic presentation of transthyretin-related familial amyloid polyneuropathy (TTR-FAP) in Turkey

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. The mutant amyloidogenic transthyretin protein causes the systemic accumulation of amyloid fibrils that result in organ dysfunction. TTR-associated FAP is a progressive and fatal disease, if left untreated, and should be considered in the differential diagnosis of any person presenting with a progressive polyneuropathy, particularly with accompanying autonomic involvement. The clinical, electrophysiological, histopathological, and genetic characteristics of 17 patients from Turkey (5 female, 13 male) from nine families with polyneuropathy and mutations in TTR were evaluated. Sequence analysis of the TTR gene revealed five mutations (Val30Met, Glu89Gln, Gly53Glu, Glu54Gly and Gly47Glu). Mean age at disease onset was 40.4 ± 13.9 years (range 21-66 years). The most commonly reported initial complaint was paresthesia in the feet (asymmetric in three patients). Three patients (2 male) with the Glu89Gln mutation presented with carpal tunnel syndrome. Two patients with the Gly53Glu mutation showed episodes of dysarthria and hemiparesis, consistent with this genotype. Seven patients died during the period of follow-up as a result of systemic involvement. Our study suggests that a cohort of patients from Turkey with TTR-FAP exhibits clinical and genetic heterogeneity.

Status Epilepticus and Multiple Sclerosis: A Case Presentation and Literature Review:

Purpose. To search the literature for the frequency, pathogenesis, prognosis, and treatment of seizures and status epilepticus (SE) in patients with multiple sclerosis (MS). Methods. We report 2 patients with MS who presented with SE and review the literature. Results. Seizures and SE episodes worsened during MS relapses in the first patient. SE episodes and MS relapses significantly decreased after initiation of natalizumab treatment but she still had seizures and was taking 4 antiepileptic drugs (AEDs). The second patient had super refractory SE and was treated with AEDs and coma induction; SE was controlled in 1 week. Antibodies against glycine receptors were reported in her serum after her death. Conclusion. SE has been reported to remain refractory to conventional AEDs, and improve with treatment of MS relapse. Seizures often occur during MS relapses, and might be the presenting symptom of MS or the only symptom of a relapse. Patients with MS and epilepsy have been reported to have more severe MS disease courses. Seizures are refractory to treatment in patients with MS with chronic epilepsy; however, prognosis is quite good in patients experiencing provoked seizures during an MS relapse. Since some EEG findings may have prognostic value, their evaluation is invaluable for the determination of outcome. No treatment guidelines have been specified for patients with MS and SE. However, treatment with AEDs, ideally new-generation AEDs, and an MS treatment review with a new protocol will ensure a fast response to the improvement of SE.

Investigation of anti-neuronal antibodies in status epilepticus of unknown etiology: a prospective study

There have been recent reports of antibody-mediated status epilepticus. The objective of our study was to investigate the prevalence of neuronal autoantibodies in patients with status epilepticus (SE) with unresolved etiology. The presence of neuronal autoantibodies was investigated prospectively in adult patients with SE who presented to our clinic between February 2012 and December 2013 with unresolved etiology. Clinical and electrophysiologic features of seropositive patients were recorded. Also, seronegative and seropositive patient groups were compared in terms of demographic and clinical features, treatment responses, and outcomes. Neuronal antibodies against N-methyl-d-aspartate receptor (NMDA-R) were positive in 2 patients, against glycine receptor (Gly-R) in 2 patients, and against gamma-aminobutyric acid-A receptor [GABA(A)R] in 1 patient, which constituted a total of 5 (22.7%) of 22 patients with SE with unidentified etiology. One of three patients with systemic tumors was positive for GABA(A)R antibody. Four patients had a short epilepsy duration, while one of the NMDA-R antibody-positive patients had chronic epilepsy and double cortex finding in MRI. There was no significant difference between seropositive and seronegative patient groups in terms of demographic and clinical features, treatment responses, and outcomes. Neuronal antibodies are found in a sizeable portion of de novo SE patients, who are potential candidates of autoimmune encephalitis. Alternatively, these antibodies may presumably also emerge in SE patients with a chronic epilepsy history as an epiphenomenon. Further research is required to make the distinction between these two different antibody formation mechanisms.

Genotypic and phenotypic presentation of Glu89Gln mutation in Turkey

Background Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. More than 100 different mutations of the transthyretin gene are identified worldwide, but still the first described Val30Met is the most common one. The mutant amyloidogenic transthyretin protein causes systemic accumulation of amyloid fibrils that results in organ dysfunction and death. TTR-associated FAP is a progressive and fatal disease if left untreated and should be considered in the differential diagnosis of any patient with a progressive polyneuropathy, especially with an accompanying autonomic involvement.

Epilepsia partialis continua: Correlation of semiology, outcome and electrophysiologic features

OBJECTIVE Epilepsia partialis continua (EPC) is a special form of cortical epilepsy. Several studies have described the ictal and interictal electroencephalography (EEG) findings in patients with EPC; however, lateralizing and localizing values of these findings have been evaluated rarely. This study investigated the correlation of semiologic and EEG findings, and outcomes in patients with EPC. PATIENTS AND METHODS Clinical and EEG findings and outcomes, and their correlations were studied prospectively in 15 patients who were diagnosed as having EPC upon presentation to Istanbul Medical Faculty Hospital between January 2010 and April 2014, and retrospectively in 5 previously evaluated patients. RESULTS EEG findings were lateralizing in 11 (47.8%) of the overall 23 EEG recordings, 7 (30.4%) of which were also localizing. Eleven (55%) of the 20 patients had poor prognosis. Patients with interictal lateralizing EEG findings had better outcomes compared with patients who had interictal non-lateralizing EEG findings (P = 0.016). Periodic epileptiform discharges (PEDs) were noted in the 6 EEGs (3 ictal EEGs and 3 interictal EEGs) of 5 patients, all of whom had poor outcomes (P = 0.04). All four patients with false lateralizing EEG findings had poor outcomes. CONCLUSION EEG has low lateralizing and localizing value in EPC but patients with interictal lateralizing EEG findings have better outcomes, which may be used as a prognostic tool in EPC. The presence of PEDs and false lateralizing findings in EEG might be associated with poor prognosis in EPC.

A Case of Lennox-Gastaut Syndrome Who Developed Tonic Status Epilepticus Induced by Intravenous Diazepam

Summary Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy characterized by several types of seizures, special EEG patterns, and cognitive deterioration with resistance to therapy and poor prognosis. It is a well known phenomenon that some antiepileptic drugs (AED) have a worsening effect on some seizure types, especially in the generalized epilepsies of childhood. However, its underlying pathogenetic mechanisms are not fully understood. In this paper, a case with LGS who developed tonic status epilepticus induced by diazepame given intravenously is reported and the topic of seizure aggravation caused by AED and LGS is discussed.